SCHEME 1. Oxidative Chlorination of Thiols to Sulfonyl
Chlorides with TMS-Cl/KNO3
Chlorotrimethylsilane-Nitrate Salts as Oxidants:
Direct Oxidative Conversion of Thiols and
Disulfides to Sulfonyl Chlorides
G. K. Surya Prakash,* Thomas Mathew,
Chiradeep Panja, and George A. Olah*
Loker Hydrocarbon Research Institute and Department of
Chemistry, UniVersity of Southern California,
Los Angeles, California 90089-1661
et al.4 and Kim et al.5 It also has been found by Sohmiya et al.
that alkyl and aryl benzyl sulfides react with iodosobenzene
and hydrogen chloride-treated silica gel to give the correspond-
ing alkyl and aryl sulfonyl chlorides.6 This method of prepara-
tion takes longer and the reaction requires the presence of
specific functional groups such as benzyl or substituted benzyl
groups in the substrate. Use of nitrate salts with SO2Cl2 to give
the sulfonyl chloride from thiols has been reported.3f In most
of these methods the separation and purification of the products
are very tedious due to undesirable side reactions resulting in
lower selectivity and yields.
ReceiVed May 1, 2007
Herein, we report a simple and convenient method for the
direct oxidative chlorination of thiols and disulfides to the
corresponding sulfonyl chlorides using nitrate salt and chloro-
trimethylsilane as a reagent system. It is further found that
sulfides and sulfoxides under suitable conditions undergo
oxidation to their respective sulfones. In most cases, products
obtained need no further purification. Removal of the solvent
from the reaction mixture provides analytically pure product.
To utilize the oxidizing property of the “TMS-Cl/KNO3”
system, first the thiols (1a-f) were subjected to oxidation with
the TMS-Cl/nitrate salt system. Interestingly, oxidative chlorina-
tion of the substrates occurred resulting in the direct formation
of the corresponding arene sulfonyl chlorides (3a-f) in good
yields (Scheme 1). In all the cases studied arene sulfonyl
chlorides could be obtained in high purity by filtration and
evaporation of the solvent without further purification.
Since many arenesulfonyl chlorides are susceptible to hy-
drolysis during workup resulting in tedious purification proce-
A mixture of nitrate salt and chlorotrimethylsilane is found
to be a mild and efficient reagent for the direct oxidative
conversion of thiols (1) and disulfides (2) to the correspond-
ing sulfonyl chlorides (3) in excellent yields through oxida-
tive chlorination. Sulfides and sulfoxides were also found
to undergo oxidation to sulfones under similar reaction
conditions. In most cases these reactions are highly selective,
simple, and clean, affording products in high yield and purity.
Recently, we have achieved regioselective nitration of aryl-
boronic acids using chlorotrimethylsilane and nitrate salts.1 Ipso-
substituted nitroaromatics were obtained in high yields and
purity in most of these reactions. Since most of the nitrating
agents have oxidizing properties, we decided to examine the
oxidizing property of this reagent system more closely. One of
the important oxidation reactions in synthetic organic chemistry
is oxidation of sulfur compounds. Most common methods
involve the use of peroxy compounds such as peroxy acids,
hydrogen peroxide, etc. Oxidative chlorination of sulfur com-
pounds to sulfonyl chlorides serves as an important step in
organic synthesis. Sulfonyl chlorides are used in the production
of detergents, ion exchange resins, elastomers, pharmaceuticals,
dyes, herbicides, as mild alkylating agents, and as intermediates
in the production of sulfonic acid amide and esters.2 Various
methods for the oxidative chlorination of sulfur compounds
(thiols, sulfides, thioacetates, thiocarbamates, etc.) to sulfonyl
chlorides are known.3 However, many of these reactions involve
stepwise oxidation followed by chlorination giving low yields
and are not convenient and safe due to the use of hazardous
and noxious reagents.
(2) (a) Green, T. W.; Wuts, P. G. M. ProtectiVe groups in organic
Chemistry, 3rd ed.; Wiley-Interscience: New York, 1999. (b) Kociensky,
P. J. Protecting Groups; Thieme: New York, 1994. (c) Theodoridis, G.
Tetrahedron 2000, 56, 2339. (d) Brewster, J. H.; Ciotti, C. J. J. Am. Chem.
Soc. 1955, 77, 6214. (e) Blotny, G.; Biernat, J. F.; Taschner, E. Liebigs
Ann. Chem. 1963, 663, 195. (f) Moore, J. D.; Herpel, R. H.; Lichtsinn, J.
R.; Flynn, D. L.; Hanson, P. R. Org. Lett. 2003, 5, 105. (g) Dubbaka, S.
R.; Vogel, P. J. Am. Chem. Soc. 2003, 125, 15292. (h) Kværnø, L.; Werder,
M.; Hauser, H.; Carreira, E. M. Org. Lett. 2005, 7, 1145. (i) Lassalle, G.;
Galtier, D.; Galli, F. European patent 643047, 1995. (j) Lezina, O. M.;
Kuchin, A. V.; Rubtsova, S. A. Russian patent 2289574, 2006.
(3) (a) Monnee, M. C.; Marijne, M. F.; Brouwer, A. J.; Liskamp, R. M.
Tetrahedron Lett. 2000, 41, 7991. (b) Piatek, A.; Chapuis, C.; Jurczak, J.
HelV. Chim. Acta 2002, 85, 1973. (c) Humljan, J.; Gobec, S. Tetrahedron
Lett. 2005, 46, 4069. (d) Kværnø, L.; Werder, M.; Hauser, H.; Carreira, E.
M. Org. Lett. 2005, 7, 1145. (e) Meinzer, A.; Breckel, A.; Thaher, B. A.;
Manicone, N.; Otto, H.-H. HelV. Chim. Acta 2004, 87, 90. (f) Park, Y. J.;
Shin, H. H.; Kim, Y. H. Chem. Lett. 1992, 1483. (g) Schindler, W. HelV.
Chim. Acta 1957, 40, 2148. (h) Sandler, S. R.; Karo, W. In Organic
Functional group Preparations; Academic Press: New York, 1983; Vol.
I, p 630. (i) Langler, R. F. Can. J. Chem. 1976, 54, 498. (j) Grossert, J. S.;
Langler, R. F. Can. J. Chem. 1977, 55, 407. (k) Langler, R. F.; Marini, Z.
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Org. Chem. 1974, 39, 563.
Use of N-chlorosuccinimide with thiol derivatives for the
synthesis of sulfonyl chlorides has been reported by Nishiguchi
(4) Nishiguchi, A.; Maeda, K.; Miki, S. Synthesis 2006, 4131.
(5) Kim, D. W.; Ko, Y. K.; Kim, S. H. Synthesis 1992, 1203.
(1) Prakash, G. K. S.; Panja, C.; Mathew, T.; Surampudi, V.; Olah, G.
A. Org. Lett. 2004, 6, 2205.
(6) Sohmiya, H.; Kimura, T.; Fujita, M.; Ando, T. Tetrahedron 1998,
54, 13737.
10.1021/jo070907g CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/22/2007
J. Org. Chem. 2007, 72, 5847-5850
5847